Computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene
Copyright policy )Computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene
Cycline-dependent kinase 4 (CDK4), an enzyme of the cycline dependent or Ser/Thr protein kinase family, plays a role in cell cycle progression (G1 phase) by phosphorylating a tumor suppressor protein called pRB. Alteration of this enzyme due to missense mutation/ nonsynonymous single nucleotide polymorphisms (nsSNPs) are responsible for various types of cancer progression, e.g. melanoma, lung cancer, and breast cancer. Hence, this study is designed to identify the malignant missense mutation of CDK4 from the single nucleotide polymorphism database (dbSNP) by incorporating computational algorithms. Out of 239 nsSNPs; G15S, D140Y and D140H were predicted to be highly malignant variants which may have a devastating impact on protein structure or function. We also found defective binding motif of these three mutants with the CDK4 inhibitor ribociclib and ATP. However, by incorporating molecular dynamic simulation, our study concludes that the superiority of G15S than the other two mutants (D140Y and D140H) in destabilizing proteins nature.
Pulmonary and Respiratory Medicine, Cancer Research, Genotype, Science, Aminopyridines, Cancer research, Molecular Dynamics Simulation, Polymorphism, Single Nucleotide, Gene, Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer, Silent mutation, Adenosine Triphosphate, Cancer Genomics, Biochemistry, Genetics and Molecular Biology, Health Sciences, Genetics, Nonsynonymous substitution, Missense mutation, Biology, Single-nucleotide polymorphism, Genome, Q, R, Computational Biology, The p53 Signaling Network in Cancer Research, Life Sciences, Cyclin-Dependent Kinases, Genomic Landscape of Cancer and Mutational Signatures, Oncology, dbSNP, Purines, FOS: Biological sciences, Mutation, Medicine, Research Article
Pulmonary and Respiratory Medicine, Cancer Research, Genotype, Science, Aminopyridines, Cancer research, Molecular Dynamics Simulation, Polymorphism, Single Nucleotide, Gene, Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer, Silent mutation, Adenosine Triphosphate, Cancer Genomics, Biochemistry, Genetics and Molecular Biology, Health Sciences, Genetics, Nonsynonymous substitution, Missense mutation, Biology, Single-nucleotide polymorphism, Genome, Q, R, Computational Biology, The p53 Signaling Network in Cancer Research, Life Sciences, Cyclin-Dependent Kinases, Genomic Landscape of Cancer and Mutational Signatures, Oncology, dbSNP, Purines, FOS: Biological sciences, Mutation, Medicine, Research Article
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